Avaliação dos polimorfismos do TAFI e do PAI-1 e sua associação com parâmetros clínicos, bioquímicos e hemostáticos em mulheres portadoras da síndrome dos ovários policísticos

Abstract

Polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies amongst women of reproductive age. Its typical characteristics include hyperandrogenism, oligomenorrhea, anovulation and polycystic ovarian morphology that can lead to various reproductive and metabolic complications, such as insulin resistance and type 2 diabetes mellitus. In addition, women with PCOS present hemostatic disorders with damage to the fibrinolytic system, which increases the risk of cardiovascular events. Thrombin-activatable fibrinolysis inhibitor (TAFI) and Plasminogen activator inhibitor type-1 (PAI-1) play an important role in the regulation of the fibrinolytic system. Several studies have shown that women with PCOS have high levels of TAFI and PAI-1, this compromises their fibrinolytic potential, and several polymorphisms of the TAFI and PAI-1 gene have been described associated with the plasma levels of these proteins. This study was conducted in order to investigate frequencies of polymorphisms rs3742264, rs1926447 e rs940 of TAFI gene as well polymorphisms rs2227631 e rs1799889 of PAI-1 gene and their correlations with metabolic parameters, hormonal and hemostatic in women with PCOS. Ninety-seven women with PCOS diagnosed according to the Rotterdam criteria and 99 women without the syndrome (control) were selected. Venous blood samples were obtained for biochemical analysis and DNA extraction. The polymorphisms were analyzed using Polymerase Chain Reaction techniques (allele-specific PCR, PCR followed by enzyme restriction - RFLP and real-time PCR). Patients with PCOS presented elevated levels of TAFI and PAI-1. Carriers of rs940GG genotype had higher levels of TAFI in both individual evaluation of the PCOS group and the evaluation of entire population in a single group. Women with PCOS carrying AA genotype of rs2227631 polymorphism of PAI-1 gene presented higher levels of this protein compared to the control group. The multivariate logistic regression model showed an independent association of TAFI levels, testosterone and abdominal circumference in PCOS. The results suggest that plasma levels of TAFI and PAI-1 were associated with the development of PCOS, and that TAFI and PAI-1 polymorphisms influenced their plasma levels, as well as the independent association of TAFI, testosterone and circumference with the syndrome.